1. Field of the Invention
The present invention is in the field of pharmacology and specifically relates to the new use of enantiomers of morphine-like opioids, a known class of compounds, to protect central neurons from neurotoxic injury.
2. Description of the Background
The brain is exquisitely sensitive to brief hypoxia, while other tissues may survive during hypoxia for extended periods. Recently, attention has been focused on a possible role of the excitatory neurotransmitter glutamate, or related compounds, in the pathogenesis of the neuronal injury scene with a variety of brain insults, including hypoxia. Glutamate both is present at high concentrations in the mammalian central nervous system (CNS) and is toxic to central neurons. Evidence for a role of glutamate in mediating hypoxic neuronal injury is shown by the fact that certain glutamate antagonists can attenuate the acute neuronal injury produced by hypoxia, ischemia, and hypoglycemia.
The observed protective effects of glutamate antagonists on central neurons have raised the possibility that such drugs might have clinical therapeutic utility in hypoxic brain injury. However, the drugs previously known are not currently available from a clinical standpoint (e.g., have not undergone clinical trials), and little is known of their systemic effects. Furthermore, glutamate is known to be a broad-spectrum agonist with efficacy at three subtypes of excitatory amino acid receptors--kainate, quisqualate, and N-methyl-D-aspartate (NMDA). Prior to the present invention, it was not known whether blockade at one, a combination of two, or all three of the receptor subtypes was necessary to block the neurotoxicity of glutamate.
Accordingly, there remains a need for identification of pharmacologically active compounds capable of interacting with glutamate receptors to produce the desired protective effect.